ArticleThe Journal of experimental medicine2013
Signaling through C5a receptor and C3a receptor diminishes function of murine natural regulatory T cells.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
128 citing papers in PubMed, 210 citations in OpenAlex.
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- The role of the complement system in gastrointestinal-related diseases.Frontiers in immunology · 2026Review
- Innate immunity and hypertension: unveiling inflammatory pathways for novel therapies.Frontiers in pharmacology · 2026Review
- Emerging roles for complement in lung transplantation.The Journal of clinical investigation · 2025Review
- Loss ofOncotarget · 2025Article
- Subtype- and race-specific variations in the immune landscape of breast cancer: therapeutic implications.NPJ breast cancer · 2025Article
- Complement's involvement in allergic Th2 immunity: a cross-barrier perspective.The Journal of clinical investigation · 2025Review
- Immune Regulatory Crosstalk in Adipose Tissue Thermogenesis.Comprehensive Physiology · 2025Review
- Enhanced renal ischemia/reperfusion injury repair potential of exosomes derived from B7-H1Frontiers in genetics · 2025Article
- Complement and T cell activation in transplantation.Transplantation reviews (Orlando, Fla.) · 2025Review
- The Complement System.Advances in experimental medicine and biology · 2025Review
- The complement system in human pregnancy and preeclampsia.Frontiers in immunology · 2025Review
- Polyclonal antibodies selectively inhibit tumor growth and invasion and synergize with immune checkpoint inhibitors.JCI insight · 2024Article
- Article
- Th17/Treg balance: the bloom and wane in the pathophysiology of sepsis.Frontiers in immunology · 2024Review
- Targeting complement C5a to improve radiotherapy sensitivity in non-small cell lung cancer.Translational lung cancer research · 2023Article
- Complementing Testicular Immune Regulation: The Relationship between Sertoli Cells, Complement, and the Immune Response.International journal of molecular sciences · 2023Review
- The Sertoli Cell Complement Signature: A Suspected Mechanism in Xenograft Survival.International journal of molecular sciences · 2023Article
- C5aR1 blockade reshapes immunosuppressive tumor microenvironment and synergizes with immune checkpoint blockade therapy in high-grade serous ovarian cancer.Oncoimmunology · 2023Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Thymus-derived (natural) CD4(+) FoxP3(+) regulatory T cells (nT reg cells) are required for immune homeostasis and self-tolerance, but must be stringently controlled to permit expansion of protective immunity. Previous findings linking signals transmitted through T cell-expressed C5a receptor (C5aR) and C3a receptor (C3aR) to activation, differentiation, and expansion of conventional CD4(+)CD25(-) T cells (T conv cells), raised the possibility that C3aR/C5aR signaling on nT reg cells could physiologically modulate nT reg cell function and thereby further impact the induced strength of T cell immune responses. In this study, we demonstrate that nT reg cells express C3aR and C5aR, and that signaling through these receptors inhibits nT reg cell function. Genetic and pharmacological blockade of C3aR/C5aR signal transduction in nT reg cells augments in vitro and in vivo suppression, abrogates autoimmune colitis, and prolongs allogeneic skin graft survival. Mechanisms involve C3a/C5a-induced phosphorylation of AKT and, as a consequence, phosphorylation of the transcription factor Foxo1, which results in lowered nT reg cell Foxp3 expression. The documentation that C3a/C3aR and C5a/C5aR modulate nT reg cell function via controlling Foxp3 expression suggests targeting this pathway could be exploited to manipulate pathogenic or protective T cell responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.